Bioinformatics and experimental validation of MAPK pathway activation in diabetic kidney disease induced by glucose variability.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41386864", "kind": "science-record", "revision": 4, "content_hash": "sha256:bf6408586fbf1323615c72767f2819da4810cefad5fefe8deaf7056a133e9d33", "created_at": "2026-11-01T20:31:23Z", "updated_at": "2026-11-01T22:57:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics and experimental validation of MAPK pathway activation in diabetic kidney disease induced by glucose variability.", "doi": "10.1016/j.jgeb.2025.100598", "pmid": "41386864", "authors": ["Sujuan Li", "Huijuan Wang", "Yuanhang Zhang"], "journal": "Journal, genetic engineering & biotechnology", "year": 2025, "abstract": "OBJECTIVE: This article aims to evaluate the role of factors associated with oxidative stress induction in fluctuating hyperglycemia-induced diabetic kidney disease (DKD) and to elucidate the molecular mechanisms underlying the pathogenesis of DKD.\nMETHODS: We downloaded the gene expression datasets GSE30528 and GSE30529, which are associated with diabetic kidney disease (DKD), from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) and selected the top four proteins from protein-protein interaction (PPI) networks using STRING and Cytoscape software. Concurrently, we conducted diabetic animal experiments to verify that these proteins contribute to the onset and progression of DKD through oxidative stress. Finally, we confirmed the correlation and roles of these genes in the animal model.\nRESULT: The modulation of the MAPK cascade involves ITGB2 and TYROBP. The results showed that the areas under the ROC curve (AUC) for TYROBP were 0.889 and 0.966, respectively, while for ITGB2, they were 0.906 and 0.974. All other indicators had an AUC of 1.0; these indicators represent differentially expressed genes identified through data analysis. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as the levels of malondialdehyde (MDA), were measured in diabetic rats (P < 0.05). Apoptotic responses and c-Jun N-terminal kinase (JNK) activation were evident in the rat fluctuation group. Further research has demonstrated that oxidative stress regulates the MAPK pathway at both cellular and molecular levels. Gene and protein expression, particularly in the context of diabetic nephropathy, are influenced by multiple factors.\nCONCLUSION: Collectively, fluctuating hyperglycemia directly and indirectly regulates MAPK-JNK signaling via ITGB2, TYROBP, and oxidative stress, ultimately influencing the onset and progression of diabetic nephropathy.", "claims": [{"id": "claim-method", "statement": "One-way analysis of variance (ANOVA) was conducted.Variance (ANOVA) was used in conjunction with Tukey’s multiple comparison tests. This approach is primarily employed to compare single and multiple factors affecting the number of oxidative stress indicators and apoptosis in animal models. Additionally, p-JNK mRNA levels were analyzed using the Kruskal–Wallis test. Spearman’s test was applied to perform correlation analysis, a method commonly used in bioinformatics to examine gene correlations.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41386864", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "One-way analysis of variance (ANOVA) was conducted.Variance (ANOVA) was used in conjunction with Tukey’s multiple comparison tests. This approach is primarily employed to compare single and multiple factors affecting the number of oxidative stress indicators and apoptosis in animal models. Additionally, p-JNK mRNA levels were analyzed using the Kruskal–Wallis test. Spearman’s test was applied to perform correlation analysis, a method commonly used in bioinformatics to examine gene correlations."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analysed during the current study are available from the cor-responding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41386864", "locator": "sections[36] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analysed during the current study are available from the cor-responding author upon reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41386864"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE30528"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE30528"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41386864", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.jgeb.2025.100598", "sha256": 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Further research has demo", "ndialdehyde (MDA), were measured in diabetic rats (P < 0.05). Apoptotic responses and c-Jun N-", "kinase (JNK) activation were evident in the rat fluctuation group. Further research has demo", "sity (approval number wydw2022-0738). The SD rats were trained to consume chow and drinking water w"], "order_basis": "paper_text_order:1437", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["equently transferred to a −80 °C freezer for Western blotting (WB) and reverse transcription polymerase ch"], "order_basis": "paper_text_order:4414", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["he number of oxidative stress indicators and apoptosis in animal models. 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